A material analysis by an optical method uses principles such as absorbance, fluorescence, phosphorescence, chemiluminescence, reflectance, turbidity, refraction, and scattering. To analyze biomaterials using the optical principles, labels such as radioactive materials, enzymes, fluorescent materials, chemiluminescent materials, gold nanoparticles, carbon black, latex particles, and quantum dots have been mostly used. Some cases of the optical reactions generated by the labels may be detected by human eyes. However analytical apparatus have to be used for more quantitative result. Upon the optical measurement of the biomaterials, signal strength is different depending on concentrations of the biomaterials. Most of the signals are measured by setting a background for noise. To enhance the accuracy, a signal-to-noise ratio needs to be efficiently measured. To measure the signal-to-noise ratio, generally, methods such as initial calibration before the reaction is generated and background calibration may be used alone or a combination thereof may be used.
As an analytical method of biomaterials using the above-mentioned principles, there are radioimmunoassay, enzyme-linked immunosorbent assay, particle agglutination assay, chemiluminescent immunoassay, real-time polymerase chain reaction, flow cytometry, immunochromatography, etc. These methods are not limited to the analysis of materials but have been used for a disease test or diagnosis, or the like. The analytical method of biomaterials may largely be classified into homogeneous assay of performing reaction only in a solution phase and a heterogeneous assay of separating analytes or labels onto the solid phase. As the solid phase used in the heterogeneous assay, there are a plastic plate or microparticles of a polystyrene material, a nitrocellulose membrane, magnetic particles, a glass slide, etc.
The immunochromatography measures a reaction by a scheme of developing the reaction using a porous membrane as the solid phase, the gold nanoparticles or the latex particles as the labels, etc., and accumulating the labels on a test line by an antigen-antibody reaction. The immunochromatography may have easy operability and easily observe the label visually in some cases, and therefore has been very variously used for self-testing of pregnancy or ovulation, drug-of-abuse test, hemoglobin A1c test, cardiovascular disease test, infectious disease test, etc. The immunochromatography includes a control area in which it is verified whether the reaction is correctly generated in addition to a test area in which the antigen-antibody reaction is tested. If the amount of samples is small or the reaction is not generated properly, a signal may not appear in the control area and if the concentrations of the analytes in the samples are high, the signal may be reduced or may not appear in the control area due to a prozone phenomenon. Technologies related to the immunochromatography have been known in several documents such as U.S. Pat. Nos. 5,073,484, 5,591,645, 5,559,041, and 6,485,982. In addition to the immunochromatography using the porous membrane, the microfluidics for performing micromachining on a plastic surface to make a predetermined structure in which a solution may move by a capillary action is also used as a point-of care testing. The relevant example has been described in several documents such as U.S. Pat. Nos. 6,767,510 and 8,025,854.
Meanwhile, when the gold nanoparticles, the colored latex particles, or the like are used as the labels, the reaction may be tested visually. However, the visual test may not obtain the quantitative results and the test results may differ by users. It is also possible to overlook abnormal reaction due to errors by a user or accurate measurement of the reaction time. Therefore, to meet a demand for an apparatus for analyzing them, various technologies and products have been developed.
As the analytical apparatus and the analytical method, there are an apparatus and a method for capturing an image of a reaction device using an analytical apparatus including image devices such as a charge-coupled device (CCD) and a complementary metal-oxide-semiconductor (CMOS) and then analyzing a signal and noise. Currently, many products using the analytical apparatus and the analytical method have been commercialized. However, the analytical apparatus and the analytical method are hardly miniaturized because the reaction device and an imaging device need to be spaced apart from each other at a predetermined distance to secure good image quality, need to use an image device and expensive components consuming relatively larger power for image analysis.
As another example, there are an analytical apparatus and an analytical method for measuring a signal and noise using a scheme of scanning the reaction device while moving a light source and a light receiving unit (photodetector) or a scheme of scanning the reaction device while fixing a light source and a light receiving unit, upon measuring the reaction in the reaction device. The scheme of scanning, by the light source and the light receiving unit, the reaction device may use one light source and one light receiving unit to reduce errors due to a deviation of the light source or the light receiving unit, but has a disadvantage in that it needs a driving apparatus for moving the reaction device or the optical unit, and therefore is hardly miniaturized and needs to calculate background noise based on a graph of the scanning of the reaction results, and therefore makes the process complicated and difficult. On the other hand, the scheme of scanning the reaction device while fixing the light source and the light receiving unit may be miniaturized and simplify the measurement, but has a disadvantage in that the light source and the light receiving unit capable of measuring the test area or the control area and the background noise may not be easily configured and the accurate test may be made only when deviations in components of the light source and the light receiving unit are solved.
U.S. Pat. Nos. 5,580,794 and 5,837,546 describe a disposal analytical apparatus for detecting reaction on a strip using reflectance by the light-emitting diode (LED) light sources and a light receiving unit. However, the patents do not disclose an optical arrangement and a method capable of measuring background noise and therefore cannot but calculate result values only by initial calibration. In this case, the above-mentioned patents are likely to cause wrong results due to interfering materials in samples having the color such as hemoglobin or bilirubin, and may have a limited applicable range.
U.S. Pat. No. 6,235,241 discloses an analytical apparatus for detecting reaction on a strip using transmission measurement by the light-emitting diode (LED) light sources and the light receiving units but does not disclose a method for effectively calibrating the light sources and background noise and has a problem in that the analytical apparatus may not be applied to a printed circuit board (PCB) on a plane in the case of using the transmission measurement and therefore may be complicated.
U.S. Pat. No. 7,317,532 discloses an optical arrangement for detecting reaction on a strip using reflectance by an LED light source and a light receiving unit. That is, the optical arrangement is configured in a scheme of illuminating light from the LED light source which is disposed in the middle among the three LED light sources arranged in a row to the background area between the control area and the test area and then detecting the illuminated light by two light receiving units for the control area and the test area and illuminating the light from the LED light sources for the control area and the test area to the strip to transfer the reflectance results to the light receiving unit and then calibrating and calculating the signal and the noise. However, the optical arrangement uses the light receiving unit of the control area and the test area instead of the light receiving unit for the background area and therefore has a limitation in the accurate calibration.
U.S. Pat. No. 7,499,170 discloses an analytical apparatus for detecting reaction using reflectance by setting a background area on a strip by one LED light source and two light receiving units but may detect a signal only in one test area without including the control area and therefore has a problem in that the apparatus may not be suitable for detection of test errors or various tests and may be applied to only one test area.
In addition, the above-mentioned analytical apparatuses and analytical methods may not suitably reduce deviations by calibrating the light sources and the light receiving unit on the equivalent condition.
Throughout the present specification, a number of articles and patent documents are referenced and the citation thereof is disclosed. The disclosure of the cited articles and patent documents is disclosed in the present specification as a whole and thus a level of the technical field to which the present invention belongs and the contents of the present invention will be more clearly described.